Kidney Week

Abstract: FR-PO248

Optimizing Patient Enrollment in Clinical Trials Based on Albuminuria Inclusion Criteria

Session Information

• CKD: Clinical, Outcomes, Trials - II
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 1902 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Waijer, Simke W., University Medical Center Groningen, Groningen, Netherlands

Simke W. Waijer,

• Mulder, Skander, University Medical Center Groningen, Groningen, Netherlands

Skander Mulder,

• Provenzano, Michele, Second University of Naples, Naples, Italy

Michele Provenzano,

• Perkovic, Vlado, The George Institute for Global Health, Newtown, New South Wales, Australia

Vlado Perkovic,

• Lambers Heerspink, Hiddo Jan, University Medical Center Groningen, Groningen, Netherlands

Hiddo Jan Lambers Heerspink,

Background

Clinical trials in CKD enroll patients with elevated urinary albumin:creatinine ratio (UACR) levels to enrich the population for high renal risk patients. Screen failure rates are often high due to high intra-individual variability in UACR. We tested whether a screening approach with more flexible UACR thresholds would decrease screen failure rate without adversely impacting on overall study duration.

Methods

We performed a post-hoc analysis on data from the ALTITUDE trial. We selected patients randomized to placebo treatment with a baseline UACR >300 mg/g and eGFR between 30 and 60 ml/min/1.73m² at the first visit (pre-screening). We then used stepwise lower UACR cut-offs at the next qualifying visit (e.g. 300 (base scenario), 210, 150, 30 mg/g) as inclusion criteria. For each scenario we calculated the number of eligible patients and number of renal endpoints (ESRD/ doubling serum creatinine/ renal death). Based on these data we performed simulations for a future trial. We calculated the duration of enrollment and total duration of the clinical trial to accrue 961 endpoints, which provided 90% power to detect a 20% risk reduction assuming a renal event rate of 5.6% (base scenario).

Results

848 patients (median UACR 1239 mg/g; median eGFR 44 ml/min/1.73m²) were eligible for the base scenario. Lowering the UACR qualification threshold increased the number of eligible patients (thus decreasing screen failures) and resulted in only a modest decrease in average renal event rate. In simulations, lowering the UACR cut-off accelerated enrollment and did not increase overall trial duration to reach 961 events.

Conclusion

Relaxing UACR based inclusion criteria in a population with documented UACR levels in the protocol required range decreases screen failure rates without prolonging trial duration. This approach may increase recruitment feasibility and site investigators’ motivation.

Table 1